Lung Path 5 - Pulm Tumors and Pleural Diseases (Singh) Flashcards
What is more common primary pleural tumors or secondary tumors from metastasis?
Secondary from metastasis
The most frequent metastatic malignancies of the pleura arise from which 2 sites?
Breast and lung
In most metastatic involvements of the pleura what type of effusion follows?
Serous or sero-sangioneous often containing neoplastic cells
Which soft-tissue tumor has a propensity to occur in the pleura is often attached to the surface by a pedicle?
Solitary fibrous tumor
Which immunostaining features of solitary fibrous tumors are helpful in distinguishing these tumors from malignant mesotheliomas?
CD34+ and keratin-negative
What do solitary fibrous tumors show microscopically?
Whorls of reticulin and collagen fibers w/ interspersed spindle cells resembling fibroblasts
Solitary fibrous tumors are highly associated with a cryptic inverion of which chromosome and this creates which fusion gene unique to this tumor?
Chromosome 12 —> NAB2-STAT6 fusion gene
Homozygous deletion of which tumor suppressor gene occurs in about 80% of mesothelioma; involves which chromosome?
CDKN2A/INK4-α on chromosome 9p
How does malignant mesothelioma appear grossly?
Affected lung is ensheathed by a thick layer of soft, gelatinous, grayish-pink tumor tissue
What are the 3 variants of growth that can be seen microscopically with mesothelioma?
- Epithelioid
- Sarcomatoid
- Mixed
Epithelioid type of mesothelioma resembles adenocarcinoma; how can it be differentiated via immunohistochemical stains for which 5 markers?
- (+) Keratin
- (+) Calretinin
- (+) Wilms tumor 1 (WT-1)
- (+) Cytokeratin 5/6
- (+) D2-40
The mesenchymal type of mesothelioma (sarcomatoid type) appears as what type of sarcoma and resembles?
Spindle cell sarcoma, resembling fibrosarcoma
Sarcomatoid mesotheliomas may only stain positive for which marker?
Keratin
What are the typical presenting features of malignant mesothelioma?
- Chest pain
- Dyspnea
- Recurrent pleural effusions**
Malignant mesothelioma often invades lung directly and commonly metastasizes to which LN and organs?
- Hilar LN’s
- Eventually –> liver and other distant organs
What is the prognosis of malignant mesothelioma?
50% die within 12 months; few survive longer than 2 years
What are found in increased numbers in the lungs of patients with mesothelioma?
Asbestos bodies and asbestos plaques
What is the major morphological pattern of damage seen with chronic rejection following a lung transplant?
Bronchiolitis obliterans –> fibrosis causing partial or complete occlusion of small airways WITH or WITHOUT active inflammation
What age is the peak incidence of lung cancer seen?
50-60 y/o
Deletions of which 3 chromosomal loci and 3 genes are seen as early events in the squamous cell carcinoma of the lung
- 3p and 9p (site of CDKN2A gene –> product = p16)
- -* 17p (site of TP53 gene)
- -* Loss of RB tumor suppressor
Large areas of “benign” respiratory mucosa being mutagenized by exposure to carcinogens in tobacco smoke is known as what?
“Field effect“
Loss of function mutations in which 2 genes and chromosome are seen with small cell carcinoma of the lung?
- TP53
- RB
- Chromosome 3p deletions
Amplification of which gene has been associated with squamous cell carcinoma of the lung?
FGFR1
Oncogenic gain of function mutations in which 5 RTK genes are associated with Adenocarcinoma of the lung?
Tumors without RTK mutations often have mutation in which gene?
- RTK mutation = EGFR + ALK + ROS + MET and RET
- Non-RTK = KRAS
Which type of lung cancer shows the strongest association with smoking?
Small cell carcinoma
Amplification of which gene is associated with small cell carcinoma of the lung?
MYC family
Which precursor lesion is characterized by dysplastic pneumocytes lining alveolar walls that are mildly fibrotic?
Atypical adenomatous hyperplasia
Which precursor lesion is composed entirely of dysplatic cells growing confluently along pre-existing alveolar septae; and may or may not hav intracellular mucin?
Adenocarcinoma in situ
Which tumor of the lung tends to spread aerogenously, forming satellite tumors and may consolidate an entire lobe mimicking lobar pneumonia?
Mucinous ADENOCARCINOMA
What is the characteristic histologly of squamous cell carcinoma?
Keratin pearls and/or intracellular bridges
Via cytology which color will the cytoplasm be if keratin is present and is indicative of SCC?
Orange cytoplasm
Lung cancers in never smokers are more common in which sex and are most often what type of cancer?
- Women
- Adenocarcinoma
Lung cancers in never smokers are more likely to have mutations in which gene and never have mutations in what?
- More likely to have EGFR mutations; sometimes TP53
- NEVER have KRAS mutations
What is the histology of the chromatin, cytoplasm, nucleus, and nucleoli like with small cell carcinoma of the lung?
- Small cells w/ scant cytoplasm
- Finely granular (BLUE) nuclear chromatin (salt and pepper pattern)
- Absent nucleoli
- Necrosis is COMMON and often extensive
Which type of lung cancer is more commonly arising in the peripheral lung and which in the central/hilar lung?
- Peripheral = adenocarcinoma
- Central/hilar = squamous cell carcinoma
Basophilic staining of vascular walls due to encrustation by DNA from necrotic tumor cells (Azzopardi effect) is common with what lung tumor?
Small cell carcinoma
Majority of adenocarcinomas of the lung express which transcription factor required for normal lung development?
Thyroid transcription factor-1
Which type of lung tumor is almost always metastatic at time of presentation and is best treated with specific chemotherapies/radiation?
Small cell *neuroendocrine* carcinoma
What is the most aggressive lung tumor with no known preinvasive phase?
Small cell *neuroendocrine* carcinoma
What is a more ominous change squamous metaplasia or dysplasia?
Dysplasia
Which 3 markers are found in the neurosecretory granules of small cell carcinomas of the lungs?
- Chromogranin
- Synaptophysin
- CD57
Via immunohistochemistry high levels of which anti-apoptotic protein can be demonstrated in small cell carcinomas of the lung?
BCL2
Early distant spread of lung carcinoma generally occurs via which 2 pathways; which carcinoma specifically metastasizes late?
- Lymphatic and hematogenous
- Squamous cell carcinoma spreads late
What characteristic of Lambert-Eaton Syndrome distinguishes it from Myasthenia Gravis?
Sx’s IMPROVE w/ more movement throughout the day
Apical lung cancers (pancoast tumors) in the superior pulmonary sulcus tend to invade which neural structures around the trachea and produce what signs/sx’s?
- Invade cervical sympathetic plexus
- Severe pain in the distribution of the ulnar nerve
- Horner syndrome –> enophthalmos + ptosis + miosis + anhidrosis
What are the 4 favored sites of metastasis for lung carcinomas?
- Adrenals
- Liver
- Brain
- Bone
Which 3 LN’s are common sites of metastasis for lung carcinoma?
- Bronchial
- Tracheal
- Mediastinal
What may partial or total obstruction caused by a lung carcinoma cause?
- Partial –> focal emphysema
- Total –> atelectasis
Impaired drainage of the airways caused by lung carcinomas is a common cause of what?
SEVERE suppurative or ulcerative bronchitis or bronchiectasis
What is the main difference between Diffuse Idiopathic Pulmonary Neuroendocrine Cell Hyperplasia (DIPNECH) and Carcinoid tumors?
- SIZE!!!
- DIPNECH = very small, <5mm —> “Tumorlets”
- Carcinoid tumor = 5mm or larger
Venous congestion of the head and arm w/ circulatory compromise caused by an underlying lung carcinoma is known as what?
SVC syndrome
Which tumor of the lungs grows as fingerlike or spherical polypoid masses that commonly project into the lumen of the bronchus and may produce so-called collar-button lesions?
Carcinoid tumor
Which lung tumor is characterized by organoid, trabecular, palisading, ribbon, or rosette-like arrangements of cells w/ uniform round nuclei and abundant cytoplasm separated by a delicate fibrovascular stroma?
Carcinoid tumor
What are features of atypical carcinoid tumors (neuroendocrine tumor grade 2) which differ from typical carcinoid tumors (grade 1)?
- ↑↑↑ mitotic activity
- NECROSIS (typical carcinoids lack necrosis)
- Disordered growth
- ↑↑↑ rate of metastasis w/ LOWER survival
Phrenic nerve invasion by lung tumor is associated with what?
Diaphragm paralysis
Activating mutations of which gene in lung cancers is associated with a worse prognosis regardless of tx?
KRAS
Release of PTHrP leading to paraneoplastic hypercalcemia is associated with what type of lung tumor?
Squamous cell carcinoma
Which 2 hormones may be secreted by small cell carcinomas and what does each cause
- ADH —> SIADH
- ACTH —> Cushing Syndrome
What is a feature that can be seen on CXR and CT that points to metastasis TO the lung?
Multiple discrete nodules (cannonball lesions) scattered throughout all lobes
How are lung hamartomas most often discovered and how do they appear?
- Incidental finding on CXR
- Appear as rounded, radio-opacity (“coin lesion”)
What do pulmonary hamartomas consist of?
Nodules of CT; most often cartilage, also fat and fibrous tissue; intersected by epithelial clefts
Which 2 chromosomal aberrations are associated with lung hamartomas?
- 6p21
- 12q14-q15
What are 2 systemic nervous system related syndromes that may be associated with lung tumors?
- Lambert-Eaton myasthenic syndrome –> auto-abs against Ca2+ channels –> muscle weakness
- Peripheral neuropathy –> usually purely sensory
What is a dermatologic manfiestation that may be associated with lung tumors?
Acanthosis nigricans
Lymphangioleiomyomatosis is characterized by proliferation of which cells and what does this create morphologically?
Perivascular epithelioid cells –> CYSTIC, emphysema-like dilation of terminal air spaces, thickening of interstitium, and obstruction of lymph vessles
Lymphangioleiomyomatosis is associated with loss of function of which tumor suppressor; this tumor suppressor is normally a negative regulator of what?
TSC2 –> neg. regulator of mTOR activity
Diffuse involvement of both lungs with cystic, emphysem-like dilation of airspaces in Lymphangioleiomyomatosis, may present with what complication?
Pneumothorax
What are 2 hematologic abnormalities that may be assocaited with lung tumors?
- Leukemoid rxns
- Trousseau syndrome (DVT and thromboembolism)
What is a peculiar abnormality of connective tissue associated with lung tumors and what is seen with this?
Hypertrophic pulmonary osteoarthropathy –> clubbing of fingers
Lambert-Eaton Syndrome is most often associated with what tumor of the lung?
Small cell carcinoma
Trousseau sign (migratory thrombophlebitis) is most often associated with what type of lung tumor?
Adenocarcinoma
Why is it important to differentiate DIPNECH from Carcinoid tumors?
Carcinoid tumors have ability to metastasize
Immunohistochemical stains of carcinoid tumors may be positive for what 4 markers?
- Serotonin
- Neuron-specific enolase
- Calcitonin
- Bombesin
What are clinical features of carcinoid tumors which may result from their intraluminal growth?
- Persistent cough
- Hemoptysis
- Impairment of drainage of resp. pathways –> 2’ infections
- Bronchiectasis
- Emphysema
- Atelectasis
What are the sx’s of Carcinoid Syndrome?
- Flushing
- Diarrhea
- Cyanosis
What is the prognosis like for typical carcinoid vs. atypical carinoid tumors?
- Typical have 5-year survival of 95%
- Atypical have 5-year survival of 70%
Lymphangioleiomyomatosis is a lung disorder occurring almost exclusively in whom?
Young women
Which markers are expressed by Lymphangioleiomyomatosis?
Melanoma, like HMB-45 and smooth muscle cells
What is the only definitive tx currently available for Lymphangioleiomyomatosis?
Lung transplant
The strong tendency for Lymphangioleiomyomatosis to affect young women suggests what hormone contributes to proliferation of perivascular epithelioid cells?
Estrogen
Inflammatory myofibroblastic tumors, though rare, is more common in whom; presents how?
- Children
- Fever + cough + chest pain + hemoptysis
- May be asymptomatic
Imaging of a child with suspected Inflammatory myofibroblastic tumor will show what?
Single (rarely multiple) round, well-defined, peripheral mass that often has calcium deposits
Inflammatory myofibroblastic tumors are associated with activating rearrangements of which gene and on which chromosome?
ALK gene on chromosome 2p23
Growth of contiguous tumors (aka direct continuity) into the lungs most often occurs with what 2 types of tumors?
- Esophageal carcinomas
- Mediastinal lymphomas
Radiation used in therapy for tumors in the lung or mediastinum often causes what type of pleuritis?
Serofibrinous pleuritis
A purulent pleural exudate (empyema) usually results from what?
Bacterial or mycotic seeding of the pleural space; by contiguous spread from intrapulmonary infections, but may also be from lymphatic or hematogenous dissemination
Which inflammatory-type of pleural effusion is characterized by loculated, yellow-green, creamy pus composed of masses of neutrophils admixed with other leukocytes?
Empyema
Empyema of the lungs may resolve, but more often the exudate organizes into what; causes what complications?
- Organizes –> dense, tough fibrous adhesions
- Frequently obliterate the pleural space or envelope the lungs
- Restricting pulmonary expansion
What are the 3 major mechanisms underlying transudative pleural effusions; examples?
- ↑ hydrostatic pressure; “overflow” from the lung interstitium = CHF
- ↓ plasma oncotic pressure = nephrotic syndrome
- Movement of transudative ascitic fluid thru the diaphargam = cirrhosis
What are the 2 major mechanisms underlying exudative pleural effusions; some examples?
- Inflammation –> infection (TB, pneumonia), PE (infarction), CT disease (SLE, RA), adjacent to subdiaphragmatic disease (pancreatitis, subphrenic abscess)
- Malignancy
What is the arrow indicating on this CT scan?
Pleural effusion
How will a pleural effusion associated with mediastinal carcinomatosis appear grossly due to decreased lymph drainage?
Milky chylous effusion = Chylothorax
Noninflammatory collections of serous fluid within pleural cavities are known as what; appear how grossly?
Hydrothorax; clear fluid that is straw colored
What is the most common cause of hydrothorax; other causes?
- Most common = Cardiac failure
- Also, renal failure and cirrhosis
Which type of pleuritis is manifested by sanguineous inflammatory exudates?
Hemorrhagic pleuritis
Hemorrhagic pleuritis is found in what 3 settings?
- Hemorrhagic diatheses
- Rickettsial diseases
- Neoplastic involvement
Spontaneous idiopathic penumothorax most often occurs in which age group and is due to what?
- Young patients
- Rupture of small, peripheral, usually apical subpleural blebs
When injury to chest wall results in a one-way valve allowing air into the pleural space, but not out, effectively acting as a pump and ↑ pressure, this is known as?
Tension pneumothorax
A tension pneumothorax is due to expansion of which structure?
Chest wall (not lungs per se)
What is one of the more devastating consequences of Empyema that makes it hard to treat and hard to clear out?
Creating loculations –> web-like traps for fluid
What type of pneumothorax is this?
Primary pneumothorax
What type of pneumothorax is this?
Tension pneumothorax
Which type of pneumothorax is associated with pleural cavity pressure is < atmospheric pressure?
Pleural cavity pressure > atmospheric pressure?
- Pleural cavity < atmospheric = primary pneumothorax
- Pleural cavity > atmospheric = tension pneumothorax
In spontaneous idiopathic pneumothorax which direction will the trachea shift?
TOWARD the side of collapse
Which soft-tissue tumor has a propensity to occur in the pleura is often attached to the surface by a pedicle?
Solitary fibrous tumor
What do solitary fibrous tumors show microscopically?
Whorls of reticulin and collagen fibers w/ interspersed spindle cells resembling fibroblasts
Hemothorax is a usually fatal complication associated with what?
Ruptured aortic aneurysm or vascular trauma
How does malignant mesothelioma appear grossly?
Affected lung is ensheathed by a thick layer of soft, gelatinous, grayish-pink tumor tissue
What are the 3 variants of growth that can be seen microscopically with mesothelioma?
- Epithelioid
- Sarcomatoid
- Mixed
Epithelioid type of mesothelioma resembles adenocarcinoma; how can it be differentiated via immunohistochemical stains for which 5 markers?
- (+) Keratin
- (+) Calretinin
- (+) Wilms tumor 1 (WT-1)
- (+) Cytokeratin 5/6
- (+) D2-40
Pneumothorax is most commonly associated with what 3 conditions?
- Emphysema
- Asthma
- Tuberculosis
Typical course of spontaneous idiopathic penumothorax; and likelihood or recurrence?
- Typically subsides spontaneously as air is resorbed
- Reccurent attacks = common
